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Transcript of Cholinergic drugs thea
Cholinergic Drugs and Related Agents
Mimic the action of acetylcholine or,Blocks the action of acetylcholine (ACh)
*Cholinergc Drugs - stimulates the parasympathetic nervous system (rest and digest).
Acetylcholineis one of many
neurotransmitters in the autonomic nervous system (ANS)
only neurotransmitter used in the motor division of the somatic nervous system
Nicotinic Receptorscoupled directly to ion channelsfirst neurotransmitter isolated and purified in an active
formIt is a glycoprotein embedded into the polysynaptic
membrane that can be obtained from the electric organs of the marine ray, Torpedo californica and the electric eel, Electrophorus electricus.
When the neurotransmitter ACh binds to the nicotinic receptor, it causes a change in the permeability of the membrane to allow passage of small cations Ca2, Na, and K. This depolarization results in muscular contraction at a neuromuscular junction or, as occurs in autonomic ganglia, continuation of the nerve impulse.
Nicotinic receptor subtypes
N1 N2
At the neuromuscular junction Found in autonomic ganglia
blocked by succinycholine, d-tubocurarine, and decamethonium and stimulated by phenyltrimethylammonium
blocked by hexamethonium and trimethaphan but stimulated by tetramethylammonium and dimethyl 4-phenylpiperazinium
Muscarinic Receptors
play an essential role n regulating the function of organs innervated by the autonomic nervous system to maintain homeostasis.
Its action can result to stimulation/inhibition of the organ system that is affected.
Muscarinic Receptor subtypesM-
receptors subtypes
M1 M2 M3 M4 M5
Other name
neural Cardiac muscarinic receptors
Glandular muscarinic receptors
Location Exocrine glands and autonomic ganglia
Atria and conducting tissue of the heart
Exocrine glands and smooth muscle
CNS Substantia nigra (cns)
Function Affects arousal attention, REM, emotional response, affective disorder
Cardiac inhibition
Lacrimal, salivaryMostly stimulatory effect
Direct regulatory action on K and Ca ion channels
May regulate dopamine release at terminals within the striatum
Cholinergic NeurochemistryCholinergic neurons synthesize, stores and releases
ACh . It describes any neuron which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages.
Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and are known for their role in promoting cortical activation during both wakefulness and during rapid eye movement (REM) sleep.
Neurochemistry is the specific study of neurochemicals including neurotransmitters and other molecules (such as psychopharmaceuticals) that influence the function of neurons.
CHOLINERGIC AGONISTcholinergic agents; parasympathomimetic; mimics effect of parasympathetic nervous system
neuroransmittersA substance (or ligand) is cholinergic if it is capable of
producing, altering, or releasing acetylcholine ("indirect-acting") or mimicking its behaviour at one or more of the body's acetylcholine receptor types ("direct-acting").
Cholinergic Stereochemistryis the study of the chemistry involved in the relative
spatial arrangement of cholinergic atoms and molecules.
Has 3 techniques
X-ray crystallographyis a method of
determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and diffracts into many specific directions.
Nuclear magnetic resonance a physical phenomenon in
which nuclei in a magnetic field absorb and re-emit electromagnetic radiation.
This energy is at a specific resonance frequency which depends on the strength of the magnetic field and the magnetic properties of the isotope of the atoms
Molecular Modelling by computation
encompasses all theoretical methods and computational techniques used to model or mimic the behavior of molecules.
STRUCTURE – ACTIVITY RELATONSHIPS
is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism.
ProductsOxotremorine[1-(pyrrolidono)-4-
pyrrolidino- 2-butyne]CNS muscarinic
stimulantStudied to be a drug
treatment on Alzheimer’s disease
CHOLINERGIC RECEPTOR ANTAGONISTSblocks the neurotransmitter acetylcholine in
the central and the peripheral nervous system. cholinergic blockers, parasympatholytics or anticholinergic
Cholinesterase inhibitorsbind to cholinesterase resulting in increased
acetylcholine in the synapses, causing increased parasympathetic activity
Acetylcholinesterase - an enzyme that rapidly breaks down the neurotransmitter, acetylcholine, so that it does not over-stimulate post-synaptic nerves, muscles, and exocrine glands
Acetylcholinesterase inhibitor - a chemical that binds to the enzyme, cholinesterase, and prevents it from breaking down the neurotransmitter, acetylcholine.
2 types of cholinesterase:Acetylcholinesterase (AChE) – its inhibition
prolongs the duration of the neurotransmitter in the junction and produces pharmacological effects similar to those observed when ACh is administered.
Butyrylcholinesterase (BuChE) – (pseudocholinesterase), is located in human plasma. Has catalytic property similar to AChE
2 TYPES OF ACETYCHOLINETRANFERASE INHIBITORS
REVERSIBLE INHIBITORS– has therapeutic application
IRREVERSIBLE INHIBITORS – these chemicals are nerve poisons and had been use in warfare, bioterrorism, and as agricultural insecticides. They permit ACh to accumulate at nerve endings and exacerbate ACh-like actions.
Physostigmine, USP
Physostigma venemosum.topical application in the
treatment of glaucomaantidote for atropine
poisoning and other antcholinergic drugs.
Neostigmine Bromide - antidote to
nondepolarizing neuromuscular blocking drugs
treatment of myasthenia gravis.
Demecarium bromide, USP – long acting miotic use
to treat wide angle glaucoma and accommodative esotropia.
GalantamineLeucojum aestivum
belonging to the Amaryllidaceae family and from the bulbs of the daffodil, Narcissus pseudonarcissus;
no effect on butyrylcholinesterase; acts at allosteric nicotinic sites, further enhancing its cholinergic activity.
Rivastigmine – the FDA approved its
use in mild-to-moderate Alzheimer’s disease in April 2000.
In July 2007, it was granted approval for use in managing mild-to-moderate dementia associated with Parkinson’s disease.
Irrevrsible InhibitorsIsofluorphate, USP(Floropryl) - Stable in
peanut oil (1 yr).Solutions in peanut oil
can be sterilized by autoclaving;
Should be stored in glass containers, discoloration when decomposed;
treatment of glaucoma
Malathion - Water insoluble
phophodithioate esterused as agricultural
insecticide; generally, cause
poisoning only by ingestion of large doses.
Parathion - (Thipos); Decomposed at pH
above 7.5; causes poisoning by
inhalation or dermal absorption;
Used as an agrcultural insecticide
Hexaethyltetraphosphate (HETP) and Tetraethylpyrophosphate (TEPP) - Developed by the Germans
during WWII; Insecticide against aphids;
Fruit trees or vegetables sprayed retain no harmful residue after a period of a few days or weeks, depending on the weather conditions.;
Workers spraying with these agents should use extreme caution so that vapors are not breathed and none of the vapor or liquid comes in contact with the eyes or skin.
CHOLINERGIC BLOCKING AGENTS
Anticholinergic action by drugs and chemicals apparently depends on their ability to reduce the number of free receptors that can interact with Ach.
Some theories indicate that the amount of drug-receptor complex formed at a given time depends on the affinity of the drug for the receptor and that a drug that acts as an agonist must also possess another property called efficacy or intrinsic activity.